The Collatz Conjecture and Integers of the Form \u3cem\u3e2\u3csup\u3ek\u3c/sup\u3eb−m\u3c/em\u3e and \u3cem\u3e3\u3csup\u3ek\u3c/sup\u3eb−1\u3c/em\u3e

One of the more well-known unsolved problems in number theory is the Collatz (3n + 1) Conjecture. The conjecture states that iterating the map that takes even n ∈ N to n/2 and odd n to (3n+1)/2 will eventually yield 1. This paper is an exploration of this conjecture on positive integers of the form 2kb−m and 3kb−1, and stems from the work of the first author\u27s Senior Seminar research. We take an elementary approach to prove interesting relationships and patterns in the number of iterations, called the total stopping time, required for integers of the aforementioned forms to reach 1, so that our results and proofs would be accessible to an undergraduate. Our results, then, provide a degree of insight into the Collatz Conjecture

Proteasomal regulation of the mutagenic translesion DNA polymerase, Saccharomyces cerevisiae Rev1

Translesion DNA synthesis (TLS) functions as a tolerance mechanism for DNA damage at a potentially mutagenic cost. Three TLS polymerases (Pols) function to bypass DNA damage in Saccharomyces cerevisiae: Rev1, Pol ζ, a heterodimer of the Rev3 and Rev7 proteins, and Pol η (Rad30). Our lab has shown that S. cerevisiae Rev1 protein levels are under striking cell cycle regulation, being ~50-fold higher during G2/M than during G1 and much of S phase (Waters and Walker, 2006). REV1 transcript levels only vary ~3-fold in a similar cell cycle pattern, suggesting a posttranscriptional mechanism controls protein levels. Here, we show that the S. cerevisiae Rev1 protein is unstable during both the G1 and the G2/M phases of the cell cycle, however, the protein's half-life is shorter in G1 arrested cells than in G2/M arrested cells, indicating that the rate of proteolysis strongly contributes to Rev1's cell cycle regulation. In the presence of the proteasome inhibitor, MG132, the steady-state levels and half-life of Rev1 increase during G1 and G2/M. Through the use of a viable proteasome mutant, we confirm that the levels of Rev1 protein are dependent on proteasome-mediated degradation. The accumulation of higher migrating forms of Rev1 under certain conditions shows that the degradation of Rev1 is possibly directed through the addition of a polyubiquitination signal or another modification. These results support a model that proteasomal degradation acts as a regulatory system of mutagenic TLS mediated by Rev1.National Institute of Environmental Health Sciences (Grant 5-R01-ES015818)National Institute of Environmental Health Sciences (Grant P30 ES002109

The Digital Learning Laboratory Model to Catalyze Change in University Teaching and Learning

This paper outlines a unique model catalyzing change in teaching and learning known as the Digital Learning Laboratory (DLL) model that a large research university in the northeastern United States currently employs. We focus here on the MOOC work that the individuals in the DLL lead that have spread to improvements in teaching practices and learning experiences across departments beyond MOOCs. We discuss the MOOC development process and the ways in which this process can differ greatly from the development of an in-person course creating the initial and continued need for the DLL. Then, we describe the Digital Learning Laboratory, a community of practice of academics with advanced degrees in their field of specialization and housed in the relevant departments across our university. Finally, we discuss potential advantages of this model, including having a person with subject-matter expertise leading MOOC and hybrid projects and thereby not requiring a different tenure-track faculty member to learn MOOC development skills for each new course.Sandland, JG.; Wiltrout, ME. (2020). The Digital Learning Laboratory Model to Catalyze Change in University Teaching and Learning. En 6th International Conference on Higher Education Advances (HEAd'20). Editorial Universitat Politècnica de València. (30-05-2020):275-282. https://doi.org/10.4995/HEAd20.2020.1103827528230-05-202

Misacylation of tRNA with methionine in Saccharomyces cerevisiae

Accurate transfer RNA (tRNA) aminoacylation by aminoacyl-tRNA synthetases controls translational fidelity. Although tRNA synthetases are generally highly accurate, recent results show that the methionyl-tRNA synthetase (MetRS) is an exception. MetRS readily misacylates non-methionyl tRNAs at frequencies of up to 10% in mammalian cells; such mismethionylation may serve a beneficial role for cells to protect their own proteins against oxidative damage. The Escherichia coli MetRS mismethionylates two E. coli tRNA species in vitro, and these two tRNAs contain identity elements for mismethionylation. Here we investigate tRNA mismethionylation in Saccharomyces cerevisiae. tRNA mismethionylation occurs at a similar extent in vivo as in mammalian cells. Both cognate and mismethionylated tRNAs have similar turnover kinetics upon cycloheximide treatment. We identify specific arginine/lysine to methionine-substituted peptides in proteomic mass spectrometry, indicating that mismethionylated tRNAs are used in translation. The yeast MetRS is part of a complex containing the anchoring protein Arc1p and the glutamyl-tRNA synthetase (GluRS). The recombinant Arc1p-MetRS-GluRS complex binds and mismethionylates many tRNA species in vitro. Our results indicate that the yeast MetRS is responsible for extensive misacylation of non-methionyl tRNAs, and mismethionylation also occurs in this evolutionary branc

The Burden of Mood and Anxiety Disorders during the COVID-19 Pandemic: A Narrative Literature Review of Risk Factors

Since the first case of novel coronavirus disease 2019 (COVID-19) was diagnosed in December 2019, it has rapidly spread across nations and stimulated global public health action. In order to mitigate the spread of COVID-19, policies have been implemented in order to enforce physical distancing (or social distancing). Although clinically necessitated to prevent transmission of COVID-19, these policies have psychological secondary effects including loneliness and social isolation. The aim of this narrative literature review is to understand the prevalence of mood and anxiety disorders during the COVID-19 pandemic as well as associated risk factors. A literature search was conducted on studies published between March 1, 2020 and March 15, 2021. A total of 20 articles were selected for inclusion. All studies included in this review found an increase in mood and anxiety disorder prevalence in communities across the world, particularly impacting those who are Hispanic, women, young, low-income, as well as those who exhibit low distress tolerance and low resilience. This increased prevalence of mental health conditions during the COVID-19 pandemic may have public health repercussions in subsequent years, including increased morbidity and mortality. A shift from individual-level to population health approaches for mental health treatment is critical in the context of the COVID-19 pandemic

Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged mice.

Aging is a contributing factor in cancer occurrence. We recently demonstrated that systemic immunotherapy (IT) administration in aged, but not young, mice resulted in induction of rapid and lethal cytokine storm. We found that aging was accompanied by increases in visceral fat similar to that seen in young obese (ob/ob or diet-induced obese [DIO]) mice. Yet, the effects of aging and obesity on inflammatory responses to immunotherapeutics are not well defined. We determine the effects of adiposity on systemic IT tolerance in aged compared with young obese mice. Both young ob/ob- and DIO-generated proinflammatory cytokine levels and organ pathologies are comparable to those in aged ad libitum mice after IT, culminating in lethality. Young obese mice exhibited greater ratios of M1/M2 macrophages within the peritoneal and visceral adipose tissues and higher percentages of TNF(+) macrophages in response to αCD40/IL-2 as compared with young lean mice. Macrophage depletion or TNF blockade in conjunction with αCD40/IL-2 prevented cytokine storms in young obese mice and protected from lethality. Calorie-restricted aged mice contain less visceral fat and displayed reduced cytokine levels, protection from organ pathology, and protection from lethality upon αCD40/IL-2 administration. Our data demonstrate that adiposity is a critical factor in the age-associated pathological responses to systemic anti-cancer IT

Administration of either anti-CD40 or interleukin-12 following lethal total body irradiation induces acute lethal toxicity affecting the gut

AbstractInterleukin (IL)-12 and antibodies against CD40 have demonstrated antitumor effects in a variety of in vivo model systems. However, both agents can also mediate significant toxicities either when used following lethal TBI or when administered in combination with other agents such as IL-2. In this study, we assessed the effects of anti-CD40 monoclonal antibody (MoAb) and IL-12 in lethally irradiated mice. Acute lethal toxicity was observed following the administration of either 10 microg anti-CD40 MoAb (FGK45) or 0.5 microg of recombinant murine (rm)IL-12 that resulted in 100% mortality of all mice within 4 to 6 days. Histological evaluation revealed destruction of the normal gut architecture in both anti-CD40 MoAb- and rmIL-12-treated mice. Analysis of serum cytokine levels in the lethally irradiated mice receiving anti-CD40 MoAb demonstrated a marked increase of interferon (IFN)-gamma and IL-12 p40, whereas mice receiving rmIL-12 demonstrated a marked increase of IFN-gamma. Lethally irradiated IL-12 p40 knock-out mice were resistant to anti-CD40-induced toxicity, suggesting that the lack of IL-12 p40 with no possibility of making functional IL- 12 p70 is key for this toxic reaction. Similarly, lethally irradiated IFN-gamma knock-out mice were completely resistant to rmIL-12-induced toxicity, suggesting that IFN-gamma is a major player in IL-12-mediated toxicity. These results suggest that both anti-CD40 MoAb and rmIL-12 induce an acute fatal toxicity characterized by similar intestinal pathology and mediated in part by IFN-gamma.Biol Blood Marrow Transplant 2002;8(6):316-25

Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (Trail) Contributes to Interferon γ–Dependent Natural Killer Cell Protection from Tumor Metastasis

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is expressed by in vitro activated natural killer (NK) cells, but the relevance of this observation to the biological function of NK cells has been unclear. Herein, we have demonstrated the in vivo induction of mouse TRAIL expression on various tissue NK cells and correlated NK cell activation with TRAIL-mediated antimetastatic function in vivo. Expression of TRAIL was only constitutive on a subset of liver NK cells, and innate NK cell control of Renca carcinoma hepatic metastases in the liver was partially TRAIL dependent. Administration of therapeutic doses of interleukin (IL)-12, a powerful inducer of interferon (IFN)-γ production by NK cells and NKT cells, upregulated TRAIL expression on liver, spleen, and lung NK cells, and IL-12 suppressed metastases in both liver and lung in a TRAIL-dependent fashion. By contrast, α-galactosylceramide (α-GalCer), a powerful inducer of NKT cell IFN-γ and IL-4 secretion, suppressed both liver and lung metastases but only stimulated NK cell TRAIL-mediated function in the liver. TRAIL expression was not detected on NK cells from IFN-γ–deficient mice and TRAIL-mediated antimetastatic effects of IL-12 and α-GalCer were strictly IFN-γ dependent. These results indicated that TRAIL induction on NK cells plays a critical role in IFN-γ–mediated antimetastatic effects of IL-12 and α-GalCer

Nanostructured Nickel Phosphide as an Electrocatalyst for the Hydrogen Evolution Reaction

Nanoparticles of nickel phosphide (Ni_2P) have been investigated for electrocatalytic activity and stability for the hydrogen evolution reaction (HER) in acidic solutions, under which proton exchange membrane-based electrolysis is operational. The catalytically active Ni_2P nanoparticles were hollow and faceted to expose a high density of the Ni_2P(001) surface, which has previously been predicted based on theory to be an active HER catalyst. The Ni2P nanoparticles had among the highest HER activity of any non-noble metal electrocatalyst reported to date, producing H_2(g) with nearly quantitative faradaic yield, while also affording stability in aqueous acidic media